Antiretroviral Therapy in Severely Malnourished, HIV-infected Children in Asia

doi:10.1097/INF.0000000000001074

Observational Study

. 2016 May;35(5):e144-51.

doi: 10.1097/INF.0000000000001074.

Antiretroviral Therapy in Severely Malnourished, HIV-infected Children in Asia

David C Boettiger¹, Linda Aurpibul, Dina Mukiarti Hudaya, Siew M Fong, Pagakrong Lumbiganon, Vonthanak Saphonn, Khanh H Truong, Rawiwan Hansudewechakul, Lam V Nguyen, Viet C Do, Torsak Bunupuradah, Kulkanya Chokephaibulkit, Nik Khairulddin Nik Yusoff, Nagalingeswaran Kumarasamy, Dewi Kumara Wati, Kamarul Azahar Razali, Azar Kariminia; TREAT Asia Pediatric HIV Observational Database

Collaborators, Affiliations

Collaborators

TREAT Asia Pediatric HIV Observational Database:
C V Mean, V Saphonn, S Sarun, J Tucker, F J Zhang, N Kumarasamy, S Saghayam, E Chandrasekaran, D K Wati, L P P Atmikasari, I Y Malino, N Kurniati, D Muktiarti, S M Fong, M Thien, M Lim, F Daut, N K Nik Yusoff, P Mohamad, K A Razali, T J Mohamed, N F Abdul Rahman, N A D R Mohammed, R Nallusamy, K C Chan, T Sudjaritruk, V Sirisanthana, L Aurpibul, P Oberdorfer, R Hansudewechakul, S Denjanta, W Srisuk, A Kongphonoi, P Lumbiganon, P Kosalaraksa, P Tharnprisan, T Udomphanit, G Jourdain, T Bunupuradah, T Puthanakit, W Prasitsuebsai, W Chanthaweethip, K Chokephaibulkit, K Lapphra, W Phongsamart, S Sricharoenchai, K H Truong, Q T Du, C H Nguyen, V C Do, T M Ha, V T An, L V Nguyen, K D T Khu, A N Pham, L T Nguyen, O N Le, A H Sohn, N Durier, C Sethaputra, D A Cooper, M G Law, A Kariminia

Affiliation

¹ From the *The Kirby Institute, UNSW Australia, Sydney, Australia; †Department of Pediatrics, Faculty of Medicine, Chiang Mai University and Research Institute for Health Sciences, Chiang Mai, Thailand; ‡Cipto Mangunkusumo General Hospital, Jakarta, Indonesia; §Hospital Likas, Kota Kinabalu, Malaysia; ¶Division of Infectious Diseases, Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; ‖National Centre for HIV/AIDS Dermatology and STDs, Phnom Penh, Cambodia; **Children's Hospital 1, Ho Chi Minh City, Vietnam; ††Chiangrai Prachanukroh Hospital, Chiang Rai, Thailand; ‡‡National Hospital of Pediatrics, Hanoi, Vietnam; §§Children's Hospital 2, Ho Chi Minh City, Vietnam; ¶¶HIV-NAT, the Thai Red Cross AIDS Research Centre, Bangkok, Thailand; ‖‖Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; ***Hospital Raja Perempuan Zainab II, Kelantan, Malaysia; †††YRGCARE Medical Centre, CART CRS, Chennai, India; ‡‡‡Sanglah Hospital, Udayana University, Bali, Indonesia; §§§Pediatric Institute, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia; and ¶¶¶Members of TREAT Asia Pediatric HIV Observational Database are listed in Appendix.

PMID: 26835972
PMCID: PMC4829479
DOI: 10.1097/INF.0000000000001074

Observational Study

Antiretroviral Therapy in Severely Malnourished, HIV-infected Children in Asia

David C Boettiger et al. Pediatr Infect Dis J. 2016 May.

. 2016 May;35(5):e144-51.

doi: 10.1097/INF.0000000000001074.

Authors

Collaborators

TREAT Asia Pediatric HIV Observational Database:
C V Mean, V Saphonn, S Sarun, J Tucker, F J Zhang, N Kumarasamy, S Saghayam, E Chandrasekaran, D K Wati, L P P Atmikasari, I Y Malino, N Kurniati, D Muktiarti, S M Fong, M Thien, M Lim, F Daut, N K Nik Yusoff, P Mohamad, K A Razali, T J Mohamed, N F Abdul Rahman, N A D R Mohammed, R Nallusamy, K C Chan, T Sudjaritruk, V Sirisanthana, L Aurpibul, P Oberdorfer, R Hansudewechakul, S Denjanta, W Srisuk, A Kongphonoi, P Lumbiganon, P Kosalaraksa, P Tharnprisan, T Udomphanit, G Jourdain, T Bunupuradah, T Puthanakit, W Prasitsuebsai, W Chanthaweethip, K Chokephaibulkit, K Lapphra, W Phongsamart, S Sricharoenchai, K H Truong, Q T Du, C H Nguyen, V C Do, T M Ha, V T An, L V Nguyen, K D T Khu, A N Pham, L T Nguyen, O N Le, A H Sohn, N Durier, C Sethaputra, D A Cooper, M G Law, A Kariminia

Affiliation

¹ From the *The Kirby Institute, UNSW Australia, Sydney, Australia; †Department of Pediatrics, Faculty of Medicine, Chiang Mai University and Research Institute for Health Sciences, Chiang Mai, Thailand; ‡Cipto Mangunkusumo General Hospital, Jakarta, Indonesia; §Hospital Likas, Kota Kinabalu, Malaysia; ¶Division of Infectious Diseases, Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; ‖National Centre for HIV/AIDS Dermatology and STDs, Phnom Penh, Cambodia; **Children's Hospital 1, Ho Chi Minh City, Vietnam; ††Chiangrai Prachanukroh Hospital, Chiang Rai, Thailand; ‡‡National Hospital of Pediatrics, Hanoi, Vietnam; §§Children's Hospital 2, Ho Chi Minh City, Vietnam; ¶¶HIV-NAT, the Thai Red Cross AIDS Research Centre, Bangkok, Thailand; ‖‖Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; ***Hospital Raja Perempuan Zainab II, Kelantan, Malaysia; †††YRGCARE Medical Centre, CART CRS, Chennai, India; ‡‡‡Sanglah Hospital, Udayana University, Bali, Indonesia; §§§Pediatric Institute, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia; and ¶¶¶Members of TREAT Asia Pediatric HIV Observational Database are listed in Appendix.

PMID: 26835972
PMCID: PMC4829479
DOI: 10.1097/INF.0000000000001074

Abstract

Background: Information on antiretroviral therapy (ART) use in HIV-infected children with severe malnutrition (SM) is lacking. We investigated long-term ART outcomes in this population.

Methods: Children enrolled in the TREAT Asia Pediatric HIV Observational Database who had SM (weight-for-height or body mass index-for-age Z score less than -3) at ART initiation were analyzed. Generalized estimating equations were used to investigate poor weight recovery (weight-for-age Z score less than -3) and poor CD4% recovery (CD4% <25), and competing risk regression was used to analyze mortality and toxicity-associated treatment modification.

Results: Three hundred fifty-five (11.9%) of 2993 children starting ART had SM. Their median weight-for-age Z score increased from -5.6 at ART initiation to -2.3 after 36 months. Not using trimethoprim-sulfamethoxazole prophylaxis at baseline was associated with poor weight recovery [odds ratio: 2.49 vs. using; 95% confidence interval (CI): 1.66-3.74; P < 0.001]. Median CD4% increased from 3.0 at ART initiation to 27.2 after 36 months, and 56 (15.3%) children died during follow-up. More profound SM was associated with poor CD4% recovery (odds ratio: 1.78 for Z score less than -4.5 vs. -3.5 to less than -3.0; 95% CI: 1.08-2.92; P = 0.023) and mortality (hazard ratio: 2.57 for Z score less than -4.5 vs. -3.5 to less than -3.0; 95% CI: 1.24-5.33; P = 0.011). Twenty-two toxicity-associated ART modifications occurred at a rate of 2.4 per 100 patient-years, and rates did not differ by malnutrition severity.

Conclusion: Trimethoprim-sulfamethoxazole prophylaxis is important for the recovery of weight-for-age in severely malnourished children starting ART. The extent of SM does not impede weight-for-age recovery or antiretroviral tolerability, but CD4% response is compromised in children with a very low weight-for-height/body mass index-for-age Z score, which may contribute to their high rate of mortality.

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Figures

**Figure 1. Treatment response in children with severe malnutrition at treatment initiation**
Values in parentheses represent number of test results available in a)-c), and overall number of children at risk in d). Abbreviations: ART=antiretroviral therapy; WFH/BFA=weight-for-height/BMI-for-age z-score.

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Reducing Undernutrition through Counseling on Diversified Food Intake among Adult People Living with HIV on HAART, Northern Ethiopia.
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Early Height and Weight Changes in Children Using Cotrimoxazole Prophylaxis With Antiretroviral Therapy.
Boettiger DC, Muktiarti D, Kurniati N, Truong KH, Saghayam S, Ly PS, Hansudewechakul R, Van Nguyen L, Do VC, Sudjaritruk T, Lumbiganon P, Chokephaibulkit K, Bunupuradah T, Nik Yusoff NK, Wati DK, Mohd Razali KA, Fong MS, Nallusamy RA, Sohn AH, Kariminia A; Therapeutics Research, Education, and AIDS Training in Asia (TREAT Asia) Pediatric HIV Observational Database. Boettiger DC, et al. Clin Infect Dis. 2016 Nov 1;63(9):1236-1244. doi: 10.1093/cid/ciw514. Epub 2016 Jul 28. Clin Infect Dis. 2016. PMID: 27470239 Free PMC article.
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References

1. UNICEF. WHO. World Bank [6 Apr 2015];Joint child malnutrition estimates (UNICEF-WHO-WB) - Regional prevalence and numbers affected for wasting and severe wasting in 2013. Available at: http://apps.who.int/gho/data/view.wrapper.nutrition-1-5?lang=en.
1. UNAIDS [21 Feb 2014];HIV in Asia and the Pacific: UNAIDS report 2013. Available at: http://www.unaids.org/en/resources/documents/2013/name,89768,en.asp.
1. WHO [19 Feb 2014];Antiretroviral therapy of HIV infection in infants and children: towards universal access: recommendations for a public health approach - 2010 revision. Available at: http://whqlibdoc.who.int/publications/2010/9789241599801_eng.pdf. - PubMed
1. WHO [19 Feb 2014];Guidelines for an integrated approach to the nutritional care of HIV-infected children (6 months - 14 years) Available at: http://www.who.int/nutrition/publications/hivaids/9789241597524/en/ - PubMed
1. WHO. UNICEF [19 Feb 2014];Management of the child with a serious infection or severe malnutrition. Guidelines for care at the first-referral level in developing countries. Available at: http://www.who.int/maternal_child_adolescent/documents/fch_cah_00_1/en/

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[1] UNICEF. WHO. World Bank [6 Apr 2015];Joint child malnutrition estimates (UNICEF-WHO-WB) - Regional prevalence and numbers affected for wasting and severe wasting in 2013. Available at: http://apps.who.int/gho/data/view.wrapper.nutrition-1-5?lang=en.

[2] UNICEF. WHO. World Bank [6 Apr 2015];Joint child malnutrition estimates (UNICEF-WHO-WB) - Regional prevalence and numbers affected for wasting and severe wasting in 2013. Available at: http://apps.who.int/gho/data/view.wrapper.nutrition-1-5?lang=en.

[3] UNAIDS [21 Feb 2014];HIV in Asia and the Pacific: UNAIDS report 2013. Available at: http://www.unaids.org/en/resources/documents/2013/name,89768,en.asp.

[4] UNAIDS [21 Feb 2014];HIV in Asia and the Pacific: UNAIDS report 2013. Available at: http://www.unaids.org/en/resources/documents/2013/name,89768,en.asp.

[5] WHO [19 Feb 2014];Antiretroviral therapy of HIV infection in infants and children: towards universal access: recommendations for a public health approach - 2010 revision. Available at: http://whqlibdoc.who.int/publications/2010/9789241599801_eng.pdf. - PubMed

[6] WHO [19 Feb 2014];Antiretroviral therapy of HIV infection in infants and children: towards universal access: recommendations for a public health approach - 2010 revision. Available at: http://whqlibdoc.who.int/publications/2010/9789241599801_eng.pdf. - PubMed

[7] WHO [19 Feb 2014];Guidelines for an integrated approach to the nutritional care of HIV-infected children (6 months - 14 years) Available at: http://www.who.int/nutrition/publications/hivaids/9789241597524/en/ - PubMed

[8] WHO [19 Feb 2014];Guidelines for an integrated approach to the nutritional care of HIV-infected children (6 months - 14 years) Available at: http://www.who.int/nutrition/publications/hivaids/9789241597524/en/ - PubMed

[9] WHO. UNICEF [19 Feb 2014];Management of the child with a serious infection or severe malnutrition. Guidelines for care at the first-referral level in developing countries. Available at: http://www.who.int/maternal_child_adolescent/documents/fch_cah_00_1/en/

[10] WHO. UNICEF [19 Feb 2014];Management of the child with a serious infection or severe malnutrition. Guidelines for care at the first-referral level in developing countries. Available at: http://www.who.int/maternal_child_adolescent/documents/fch_cah_00_1/en/

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Antiretroviral Therapy in Severely Malnourished, HIV-infected Children in Asia

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Antiretroviral Therapy in Severely Malnourished, HIV-infected Children in Asia

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